This project will assess the contribution that analysis of the frequency and molecular nature of mutation at the HPRT gene of lymphocytes can make to the detection of genetic damage and estimation of radiation dose in populations exposed to low doses. The relative responses to radiation, including the relative persistence of response, of overall mutant frequency, the frequency of deletions affecting the HPRT gene, and the molecular character of deletions will be determined. Populations studied will be Chernobyl liquidators and Russian controls, numbering 300 each. The spectrum of deletion mutations of the HPRT gene will be defined in terms of frequency of intragenic, terminal and total gene deletions, and the extent of deletions beyond the HPRT gene. Deletions will be defined by analysis of genomic DnA of mutant lymphocyte clones, by polymerase chain reaction analysis for retention of sequences of known physical position. Sources of inter-individual variation from factors such as age, smoking, and other personal variables will be assessed, to increase the sensitivity of detection of radiation exposure. These studies will test the hypothesis that the HPRT deletion mutation spectrum provides greater specificity and sensitivity of response to radiation exposure than HPRT mutant frequency alone. Together with the biodosimetry data acquired by the other projects of this Program, these results will advance efforts to assess human risks for somatic mutation following exposure to low doses of radiation.